ELECTROPORATION OF MAMMALIAN SKIN - A MECHANISM TO ENHANCE TRANSDERMAL DRUG-DELIVERY

被引:502
作者
PRAUSNITZ, MR
BOSE, VG
LANGER, R
WEAVER, JC
机构
[1] MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139
[2] MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139
[3] MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139
关键词
STRATUM-CORNEUM; LIPID BILAYER; ELECTROPERMEABILIZATION; TISSUE; IONTOPHORESIS;
D O I
10.1073/pnas.90.22.10504
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mammalian skin owes its remarkable barrier function to its outermost and dead layer, the stratum corneum. Transdermal transport through this region occurs predominantly through intercellular lipids, organized largely in bilayers. Electroporation is the creation of aqueous pores in lipid bilayers by the application of a short (microseconds to milliseconds) electric pulse. Our measurements suggest that electroporation occurs in the intercellular lipid bilayers of the stratum corneum by a mechanism involving transient structural changes. Flux increases up to 4 orders of magnitude were observed with human skin in vitro for three polar molecules having charges between -1 and -4 and molecular weights up to slightly more than 1000. Similar flux increases were observed in vivo with animal skin. These results may have significance for drug delivery and other medical applications.
引用
收藏
页码:10504 / 10508
页数:5
相关论文
共 26 条
  • [1] RELAXATION STUDIES ON CELL-MEMBRANES AND LIPID BILAYERS IN THE HIGH ELECTRIC-FIELD RANGE
    BENZ, R
    ZIMMERMANN, U
    [J]. BIOELECTROCHEMISTRY AND BIOENERGETICS, 1980, 7 (04): : 723 - 739
  • [2] THERMODYNAMIC AND STRUCTURAL ASPECTS OF THE SKIN BARRIER
    BOUWSTRA, JA
    DEVRIES, MA
    GOORIS, GS
    BRAS, W
    BRUSSEE, J
    PONEC, M
    [J]. JOURNAL OF CONTROLLED RELEASE, 1991, 15 (03) : 209 - 220
  • [3] CHAMPION RH, 1992, TXB DERMATOLOGY
  • [4] Chang DC, 1992, GUIDE ELECTROPORATIO
  • [5] PENETRATION ENHANCEMENT FOR POLYPEPTIDES THROUGH EPITHELIA .D. ROUTES OF DELIVERY - CASE-STUDIES .6. TRANSDERMAL DELIVERY OF PEPTIDES AND PROTEINS
    CULLANDER, C
    GUY, RH
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 1992, 8 (2-3) : 291 - 329
  • [6] EPIDERMAL BARRIER FUNCTION - INTERCELLULAR LAMELLAR LIPID STRUCTURES, ORIGIN, COMPOSITION AND METABOLISM
    ELIAS, PM
    [J]. JOURNAL OF CONTROLLED RELEASE, 1991, 15 (03) : 199 - 208
  • [7] INVITRO SKIN PERMEATION TECHNIQUES
    FRIEND, DR
    [J]. JOURNAL OF CONTROLLED RELEASE, 1992, 18 (03) : 235 - 248
  • [8] FURRY JW, 1985, PREPARATION PROPERTI
  • [9] GOLDSTEIN L, 1977, INTRO COMP PHYSL
  • [10] INVITRO AND INVIVO IONTOPHORESIS OF A TRIPEPTIDE ACROSS NUDE RAT SKIN
    GREEN, P
    SHROOT, B
    BERNERD, F
    PILGRIM, WR
    GUY, RH
    [J]. JOURNAL OF CONTROLLED RELEASE, 1992, 20 (03) : 209 - 218